Phenylketonuria Serotonin

Besides being fundamental constituents of proteins they are the parent substances from which powerful hormones are derived, for example, adrenaline (epinephrine), noradrenaline (norepinephrine), thyroxine and related substances, 5-hydroxytryptamine (enteramine, serotonin), and the plant hormone indoleacetic acid. Tryptophan is also the precursor of the B vitamin nicotinic acid and hence of part of the important pyridine nucleotides. All three aromatic amino acids are potential precursors of other substances having powerful physiological activity, for example, many of the alkaloids. Errors in the metabolism of the aromatic amino acids in man can give rise to sometimes serious, but fortunately comparatively rare, disorders such as alkaptonuria and phenylketonuria. The numerous metabolic pathways involved in aromatic amino acid metabolism therefore make an important as well as an interesting study. 

Pascucci T, Ventura R, Puglisi-AUegra S, Cabib S. Deficits in biain serotonin synthesis in a genetic mouse model for phenylketonuria. Neuroreport 2002 13 2561-2564. 

Both the absence of phenylalanine hydroxylase and the block of the 5-hydroxytryptophan decarboxylase could account for the low plasma and brain serotonin observed in patients with phenylketonuria. 

The problem of pathogenesis has received more attention in the case of phenylketonuria than in most other inborn errors of metabolism. As soon as the intoxication theory was put forward, and supporting evidence in the results of dietary treatment accumulated, the search began. Early hypotheses incriminated one or other of the abnormal metabolites of phenylalanine, e.g. phenylacetic acid [63], known to affect the C.N.S., o-tyramine [64] (which probably does not occur). Several of these metabolites can inhibit such enzymes as DOPA-decarboxylase, tryptophan hydroxylase and glutamic decarboxylase of brain [65]. In fact, the concentrations of serotonin, noradrenaline and adrenaline in the blood are low in phenylketonuria [65, 66] and some theories of pathogenesis have considered that lack of these and other neurotransmitter substances at the synapses, caused by inhibition of the relevant enzyme, was the cause of the neurological disease. This was difficult to combine with the demonstrable deficiencies in... 

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